THE POSSIBLE PROTECTIVE EFFECTS OF METFORMIN ON INDOMETHACIN-INDUCED PEPTIC ULCER IN RATS

Abstract

Background: Gastric ulcer is a very common disease that represent an economic burden. Non-steroidal anti-inflammatory drugs induce ulcer in old patients and in patients with comorbidities. Indomethacin is widely used to induce gastric ulcer in animal models. Diabetic patients are highly susceptible to develop gastric ulcer. Metformin, the first line medication for the treatment of type II diabetes melilites that have many off label uses in non-diabetic patients, has been recently reported to have anti-inflammatory activities. Objectives: The present research was conducted to assess the possible healing effects of metformin on gastric ulcers induced by indomethacin in rats. Materials and methods: Thirty-six male wister rats weighing (200-250g) were used. Gastric ulcer was induced by a single oral dose of indomethacin (48mg/kg). Metformin (50,100,200mg/kg) or Omeprazole (30mg/kg) were administrated orally at single dose. Gastric juice was collected to measure gastric acidity. Stomach specimens were used in performing biochemical measurements. Results: • Indomethacin (48 mg/kg) single dose increased stomach acidity, ulcer index and induced histopathological changes. Indomethacin also decreased mucin levels and increased the activity of tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), Rho-associated protein kinas-1 (ROCK-1) and decreased the levels of the protective nitric oxide (NO). • After the induction of ulcer, rats were treated by omeprazole (30 mg/kg) or metformin (50, 100 or 200 mg/kg). • Omeprazole and metformin were found to decrease stomach acidity and ulcer index, restored the histological features and increased mucin levels. Omeprazole and metformin also decreased the levels of NF-κB, TNF-α, ROCK-1 and increased NO.

Conclusion: Metformin exerted ulcer healing effects comparable to that of omeprazole, which can be attributed, at least partly, to metformin anti-inflammatory activity and increasing NO levels.